Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia.
OBJECTIVE
The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH).


BACKGROUND
Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease.


METHODS
In a multicenter, randomized, double-blind, placebo-controlled study, 248 male and female subjects ages >or=10 and <or=17 years with HeFH were randomized to receive: step 1: simvastatin 10, 20, or 40 mg/day plus ezetimibe 10 mg/day or placebo for 6 weeks, followed by step 2: simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for 27 weeks; followed by step 3: all subjects received open-label simvastatin 10 or 20 mg/day (titrated to maximum 40 mg/day) plus ezetimibe 10 mg/day for 20 weeks. Safety was assessed throughout the study.


RESULTS
Coadministered ezetimibe and simvastatin for 6 weeks (step 1) resulted in significantly greater mean reduction in low-density lipoprotein cholesterol (LDL-C) from baseline (49.5%) compared with simvastatin monotherapy (34.4%; p < 0.01) in pooled dose groups and in individual dose groups (46.7% vs. 30.4%, 49.5% vs. 34.3%, 52.1% vs. 38.6%, respectively; p < 0.01). At 33 weeks (step 2), ezetimibe-simvastatin subjects had a mean 54.0% reduction in LDL-C compared with a mean 38.1% reduction in simvastatin monotherapy subjects (p < 0.01). At 53 weeks (step 3), the pooled reduction in LDL-C was 49.1%. All treatment regimens were well tolerated throughout 53 weeks.


CONCLUSIONS
Coadministration of ezetimibe with simvastatin was safe, well tolerated, and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks. (Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia; NCT00129402).
van der Graaf
Anouk
A
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Cuffie-Jackson
Cynthia
C
Vissers
Maud N
MN
Trip
Mieke D
MD
Gagné
Claude
C
Shi
Genming
G
Veltri
Enrico
E
Avis
Hans J
HJ
Kastelein
John J P
JJ
D000293:Adolescent; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008297:Male; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe